Neural mechanisms in asthma

Advances in the understanding of neural mechanisms in asthma may provide no vel therapeutic approaches in the treatment of asthma. Excessive activity o f cholinergic nerves may be important in asthma. Dysfunction of M-2 muscari nic receptors in asthma may lead to excessive bronchoconstriction and mucus secretion and can be induced in animal models by a range of stimuli includ ing allergen, viral infection, ozone, eosinophil products and cytokines. Ch olinergic mechanisms may be especially important in certain types of patien ts and anticholinergic agents provide protection against bronchospasm due t o psychogenic factors or beta2-blockers. Non-adrenergic non-cholinergic (NA NC) mechanisms, both inhibitory (i-NANC) and excitatory (e-NANC, may play a significant role in the pathophysiology of asthma. The putative neurotrans mitters, vasoactive interstinal polypeptide (VIP) and nitric oxide (NO), me diate neural bronchodilation in human airways. There does not appear to be a defect in the i-NANC system in moderate or severe asthma. e-NANC is media ted by the sensory neuropeptides substance P (SP) and the more potent bronc hoconstrictor neurokinin A (NKA). Various studies suggest that the SP conte nt of human airways is increased in asthma. Tachykinins are not only presen t in sensory nerves, but also are produced by inflammatory cells such as al veolar macrophages, dendritic cells, eosinophils, lymphocytes and neutrophi ls. They can be released into the airways by stimuli such as allergen and o zone. Evidence suggests that in addition to smooth muscle contraction, whic h is mediated mainly by NK2 receptors, tachykinins also cause mucus secreti on, plasma extravasation and stimulate inflammatory and immune cells. These effects are mediated by NK1 receptors. Recent studies have shown that NK2 receptor antagonists such as saredutant partially inhibit NKA-induced bronc hoconstriction in asthmatics. Thus, tachykinin receptor antagonists have po tential as therapies for asthma.